Prostate Cancer最新文献

Purpose. Increasing body mass index (BMI) is associated with higher risk prostate cancer (PC) at presentation. Whether increasing BMI also prompts earlier salvage androgen suppression therapy (sAST) is unknown. Materials and Methods. Between 1995 and 2001, 206 men with unfavorable risk PC were treated with radiation therapy (RT) or RT and six months of androgen suppression therapy in a randomized controlled trial (RCT). 108 sustained PSA failure; 51 received sAST for PSA approaching 10 ng/mL; 49 with BMI data comprised the study cohort. A multivariable Cox regression analysis identified pretreatment factors associated with earlier sAST receipt. Results. Increasing BMI prompted earlier sAST (median years: 3.7 for overweight/obese, 6.9 for normal weight; adjusted hazard ratio (AHR): 1.11; 95% CI: 1.04, 1.18; P = 0.002) as did high versus other risk PC (median: 3.2 versus 5.2 years; AHR: 2.01; 95% CI: 1.05, 3.83; P = 0.03). Increasing median time to sAST was observed for overweight/obese men with high versus other risk PC and for normal-weight men with any risk PC being 2.3, 4.6, and 6.9 years, respectively (P < 0.001 for trend). Conclusion. Increasing BMI was associated with earlier sAST. A RCT evaluating whether BMI reduction delays or eliminates need for sAST is warranted.

Aim. To compare the diagnostic performance of diffusion weighted imaging (DWI) using b-values of 1000 s/mm(2) and 2000 s/mm(2) at 3 Tesla (T) for the evaluation of clinically significant prostate cancer. Matherials and Methods. Seventy-eight prostate cancer patients underwent a 3T MRI scan followed by radical prostatectomy. DWI was performed using b-values of 0, 1000, and 2000 s/mm(2) and qualitatively analysed by two radiologists. ADC maps were obtained at b-values of 1000 and 2000 s/mm(2) and quantitatively analyzed in consensus. Results. For diagnosis of 78 prostate cancers the accuracy of DWI for the young reader was significantly greater at b = 2000 s/mm(2) for the peripheral zone (PZ) but not for the transitional zone (TZ). For the experienced reader, DWI did not show significant differences in accuracy between b-values of 1000 and 2000 s/mm(2). The quantitative analysis in the PZ and TZ was substantially superimposable between the two b-values, albeit with a higher accuracy with a b-value of 2000 s/mm(2). Conclusions. With a b-value of 2000 s/mm(2) at 3T both readers differentiated clinical significant cancer from benign tissue; higher b-values can be helpful for the less experienced readers.

Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to require androgen deprivation therapy (ADT). Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8-79.3), 49.1 months (IQR: 37.7-87.4), and 25 months (IQR: 13.1-42.8), respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03-1.25; P = 0.008) and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81-41.0; P < 0.001) were significantly associated with an increased risk of death. Conclusions. Men over the age of 76 with significant comorbidity and a PSA doubling time >2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

[This corrects the article DOI: 10.1155/2014/419801.].

Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.

Purpose. We investigated whether NS-RP increased risk of PSA failure and whether PSA should be included as a selection criterion for NS. Methods. We evaluated 357 consecutive men with screen-detected PC who underwent open RP without adjuvant radiotherapy between 9/11/2001 and 12/30/2008. Criteria for NS included Gleason score ≤3 + 4, percentage of positive biopsies (PPB) ≤50%, percentage of core involvement ≤50%, nonapical location, no perineural invasion, and no palpable disease on pre- or intraoperative exam but did not include a PSA threshold. Cox multivariable regression assessed whether increasing PSA or unilateral- or bilateral-NS versus non-NS-RP was associated with PSA failure adjusting for prognostic factors. Results. After a median follow-up of 3.96 years, 34 men sustained PSA failure (9.5%). Increasing PSA was significantly associated with increased risk of PSA failure in the interaction model (adjusted hazard ratio (AHR): 1.09 [95% CI: 1.03-1.16]; P = 0.005), whereas unilateral (AHR: 1.24 [95% CI: 0.36-4.34]; P = 0.73) or bilateral NS (AHR: 0.41 [95% CI: 0.06-2.59]; P = 0.34) versus non-NS RP was not. Conclusion. NS-RP in a screened cohort did not increase risk of PSA failure using NS criteria not including PSA.

Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa). Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score. Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%. Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival.

Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P < 0.05). There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.

Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA) compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF- β 1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF- β 1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF- β 1. The ectopic expression of SKIP inhibited both TGF- β 1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF- β 1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.